The use of percutaneous transluminal angioplasty (PTA) has become a widely accepted treatment for atherosclerosis which is accumulation of lipids (cholesterol) within the artery wall that blocks the flow of blood through the artery. PTA employs the use of a balloon catheter that is inserted into the femoral artery and guided with a wire into the coronary arteries through the aorta. The balloon portion is placed within a blocked artery and inflated. The balloon is then removed and blood flow through the artery is hopefully improved.
The use of stents in conjunction with PTA has proved beneficial in treating atherosclerosis. The first situation indicative for stent use is that in many cases the PTA procedure, by itself, is unsuccessful in producing an open lumen. Stents are also used where there is the possibility of abrupt vessel closure following the PTA. This abrupt closure is due to the artery wall expanding with the inflation of the balloon, but quickly recoiling after the removal of the intraluminal balloon pressure. The third situation is when chronic restentosis of the treated area occurs within six months to a year after the procedure. In other words, after a period of time, the cellular components within the artery wall, such as the smooth muscle cells, grow out of control and at the same time, produce components which build up much like an atherosclerotic plaque and lead to blockage of the artery. Generally, this blockage occurs within one to five years.
One of the reasons for failure of such an intravascular device is due to the formation of acute, spontaneous thrombosis, and chronic intimal, hyper-plasia. Thrombosis is initiated by platelets reacting with any non-endothelialized foreign surface to initiate a platelet plug. This plug acts as a template for the blood coagulation proteins. Over time, the platelet plug continues to grow, resulting in occlusion, or failure of the intravascular device.
Under normal circumstances, platelets circulate through the vascular system in a non-adherent state. This non-adherence is accomplished by the endothelial cells lining the vascular system. These endothelial cells have several factors which contribute to their non-thrombogenic properties. These factors include, but are not limited to, negative surface charge, the heparin sulfate in their glycocalyx, the production and release of prostacylin, adenosine diphosphate, endothelium-derived relaxing factor, and thrombomodulin. Adherence of more endothelial cells to the intravascular device leads to enhanced healing times and reduced failure rates of the device.
Problems particularly related to the use of stents during PTA procedures are acute thrombosis and chronic restentosis. Acute thrombosis may happen anywhere from two hours after implantation up to thirty days post-implantation. Clotting mechanisms generated by the human body build-up on the stent material within the blood stream and eventually lead to blockage of flow. This build-up is due primarily to the material characteristics of the stent such as surface charge and surface texture and also to the expansion of the stent. Depending upon the type of material used for the stent, the degree of thombogenicity varies. Additionally, expansion of the stent may cause acute thrombosis because of the circumferential expansion of the arterial wall which exposes the sub-endothelium tissue which is highly thrombogenic. To prevent acute thrombotic occlusion, anticoagulant therapy is required. Other problems, such as chronic restentosis or intimal hyperplasia, are typically due to a more rigid stent material contained in a compliant native artery.
The problems encountered with the use of intravascular stents are similar to those encountered with synthetic vascular grafts as discussed in U.S. Pat. Nos. 5,714,359 and 5,723,324 which are incorporated herein by reference. However, these patents only discuss modifying synthetic graft material. In particular, the systems disclosed therein are specifically for seeding luminal or inner wall surfaces of a synthetic non-conductive material and are totally incapable of providing the necessary cell coverage of an outer surface and in the intristicies between the interleaved wire materials which comprise the stent. Moreover, these patents have no appreciation of the need for carrying cell material to an outer surface of the device to be implanted or that a conductive material can be seeded.
Currently used methods for endothelial cell transplantation of stents requires the use of adhesive proteins to enhance endothelial cell adhesion to the surfaces thereof. As is known, stents are typically coated with some type of adhesive protein to make the material more attractive to endothelial cells. Current endothelial cell transplantation techniques may require up to 3 days to transplant endothelial cells and allow for morphological maturation on the surface of the stent.
Another drawback to current cell transplantation techniques is that they require the use of excessive amounts of anticoagulant, thrombolytic or smooth muscle cell antiproliferative agents which are typically delivered through drug therapy. It is also known that endothelial cells may be genetically engineered with the desired properties. However, known methods for transfection and transplation take place in two time consuming steps, typically several days, to achieve maximum efficiencies. This leads to the increased chance for contamination of the stent due to excessive handling.
Therefore, there is a need in the art to seed all surfaces of an intravascular stent with endothelial cells that may be genetically engineered to facilitate acceptance of the stent when implanted and reduce to the occurrence of chronic restentosis and acute thrombosis.